Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Thimerosal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1982

Light-induced genetic toxicity of thimerosal and benzalkonium chloride in commercial contact lens solutions.

Several commercial solutions used for daily care of contact lenses were tested for mutagenicity in 4 strains of Salmonella and for their ability to induce repairable DNA damage in the E. coli DNA polymerase A- assay. 5 of the 13 solutions tested were positive in the polymerase A- assay. These products demonstrated an increased level of genetic toxicity when the assay was conducted under conditions of illumination with visible light. Investigation of the genetic toxicity of some of their components, specifically the preservatives, indicated that thimerosal and benzalkonium chloride were capable of causing repairable DNA damage. Thimerosal was active only when the plates were incubated under conditions of illumination, and thus was light-induced. Benzalkonium chloride was active under conditions of dark incubation, and its genetic toxicity was enhanced when the plates were irradiated with visible light. These results were confirmed in a parallel experiment, in which cells were treated with the test agent and irradiated for a short period in liquid culture and viable cells then determined. None of the commercial products and none of the components tested, were mutagenic in the Salmonella assay.

Baths↗
PubMed2007

Skin reactivity to thimerosal and phenol-preserved Montenegro antigen in Brazil.

A randomized double-blind trial was performed to determine the frequency of positive reactions to the Montenegro antigen (leishmanin) preserved in thimerosal (Merthiolate) 1:10,000 or phenol 0.4%. The respective products were tested separately in 400 young healthy individuals from a non-endemic area for Leishmaniases. Each volunteer received one of the following reagents: merthiolated antigen, phenolated antigen, merthiolated saline, or phenolated saline. The frequency of positive responses to each reagent after the first application was as follows: 0% (phenolated saline), 9.2% (merthiolated saline), 34.6% (antigen in phenolated saline), and 41.1% (antigen in merthiolated saline). After 1 week, volunteers who had tested positive for merthiolated or phenolated antigen were retested with the respective preservative, while negatives were retested with the preservative they had not received during the first test. In all, 331 volunteers who received merthiolated saline during the study, of whom 41 (12.4%) tested positive. Meanwhile, 326 volunteers who received phenolated saline, 4 (1.2%) tested positive. Positive reactions in each group were similar in relation to gross appearance skin reactions. Considering the high frequency of hypersensitivity to thimerosal in the study population, it is recommended that this compound should be replaced as a preservative of the leishmanin antigen. Almost 30% of positive reactions to Montenegro antigen in what is considered a non-endemic region was surprising and will be the object of future studies.

Adolescent↗
PubMed2004

Thimerosal and autism? A plausible hypothesis that should not be dismissed.

The autism-mercury hypothesis first described by Bernard et al. has generated much interest and controversy. The Institute of Medicine (IOM) reviewed the connection between mercury-containing vaccines and neurodevelopmental disorders, including autism. They concluded that the hypothesis was biologically plausible but that there was insufficient evidence to accept or reject a causal connection and recommended a comprehensive research program. Without citing new experimental evidence, a number of observers have offered opinions on the subject, some of which reject the IOM's conclusions. In a recent review, Nelson and Bauman argue that a link between the preservative thimerosal, the source of the mercury in childhood vaccines, is improbable. In their defense of thimerosal, these authors take a narrow view of the original hypothesis, provide no new evidence, and rely on selective citations and flawed reasoning. We provide evidence here to refute the Nelson and Bauman critique and to defend the autism-mercury hypothesis.

Autistic Disorder↗
PubMed2004

Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues.

TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I(cap)) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I(cap) was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.

Animals↗
PubMed2004

Mercury concentrations in brain and kidney following ethylmercury, methylmercury and Thimerosal administration to neonatal mice.

The distribution of mercury to the brain following an injection of methylmercury (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND) 16 CD1 mice received MeHg chloride either by IM injection or by gavage. At 24 h and 7 days post-injection, total mercury concentrations were determined in blood, kidney, brain, and muscle by cold vapor atomic fluorescence spectrometry. At 24 h, an IM injection of MeHg chloride (17.4 microg) produced total mercury concentrations in the blood (6.2 +/- 0.9 microg/g), brain (5.6 +/- 1.3 microg; 0.6% delivered dose), and kidney (25.2 +/- 5.6 microg; 1.1%), approximately 30% of that obtained from oral administration (blood: 17.9 +/- 1.0 microg; brain: 16.1 +/- 1.2 microg, 1.5%; kidney: 64.9 +/- 6.3 microg, 2.7%). For comparison, PND 16 mice received an IM injection of concentrated dosing suspensions (2 microl dosing vol.) for EtHg chloride (6 microg) or Thimerosal (15.4 microg). For EtHg, approximately 0.39 +/- 0.06% of the injected mercury was detected in the brain and 3.5 +/- 0.6% in the kidney at 24 h. Thimerosal IM injection resulted in 0.22 +/- 0.04% in the brain, and 1.7 +/- 0.3% in the kidney. By 7 days, mercury levels decreased in the blood but were unchanged in the brain. An acute IM injection to adult mice of each suspension at a 10-fold higher dose resulted an average 0.1% mercury in the brain, and higher levels in the blood, kidney, and muscle as compared to the young. In immature mice, MeHg delivered via oral route of administration resulted in significantly greater tissue levels as compared to levels from IM injection. Comparisons of tissue distribution following IM administration suggest that an oral route of administration for mercury is not comparable to an IM delivery and that MeHg does not appear to be a good model for EtHg-containing compounds.

Animals↗
PubMed1995

Effect of thimerosal and other sulfhydryl reagents on calcium permeability in thymus lymphocytes.

We have studied the effects of thimerosal, a mercurial compound extensively used as a preservative, as well as other sulfhydryl reagents (e.g. p-hydroxymercurybenzoate, hydrogen peroxide, bromophenacyl bromide, and mercuric chloride) on Ca2+ homeostasis and the redox status of sulfhydryl groups in thymus lymphocytes. They all induced an increase in [Ca2+]i which was blocked with dithiothreitol, suggesting that they act via the oxidation or blockade of sulfhydryl groups. [Ca2+]i increase could be directly related to the effect of the different reagents on cellular protein sulfhydryl content. Experiments with ethidium bromide indicate that the observed rise in [Ca2+]i was not due to a non-specific increase in membrane permeability. Thimerosal differs from the other agents studied in its oxidative properties, which is probably linked to the production of a potent reductor molecule, thiosalicylic acid, which may modulate its oxidative capacity.

Animals↗
PubMed2001

Reversed-phase high-performance liquid chromatography versus spectrophotometric assay for thimerosal in Cuban recombinant hepatitis B vaccine.

A reversed-phase liquid chromatographic method was applied to study the stability of thimerosal in Cuban recombinant hepatitis B vaccine samples stored under different temperature conditions. Salicylic acid was used as internal standard, it allowed one to determine the thimerosal in the presence of its degradation products. Good stability of the preservative was demonstrated in vaccine samples for as long as 6 years. The same results were obtained when the vaccine samples were incubated at 37 and 45 degrees C during 30 days. The results were in compliance with the microbiological test for determining the effectiveness of antimicrobial preservative in these samples.

Anti-Infective Agents↗
PubMed2001

Possible mechanisms regulating ATP- and thimerosal-induced Ca(2+) oscillations in the HSY salivary duct cell line.

The ATP-induced oscillatory changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)) were analysed in HSY cells, a salivary ductal cell line from human parotid, using a fluorescence ratio imaging system. At concentrations higher than 1 microM, ATP caused sinusoidal [Ca(2+)](i) oscillations due to the periodic release and reuptake of Ca(2+) by intracellular Ca(2+) stores. The phorbol ester 4beta-phorbol 12,13-dibutyrate (PDBu) changed the [Ca(2+)](i) oscillations to a single spike. The inhibitory effect of PDBu on the [Ca(2+)](i) signals was reversed by protein kinase C (PKC) inhibitors such as staurosporine and chelerythrine chloride. However, preincubation of the cells with the PKC inhibitors did not affect the pattern of the ATP-induced [Ca(2+)](i) oscillations. The desensitization of the [Ca(2+)](i) response observed during prolonged stimulation with ATP was also not prevented by the PKC inhibitors. Incubation of HSY cells with the sulphydryl reagent thimerosal, which enhances the sensitivity of inositol 1,4,5-trisphosphate (IP(3)) receptors, caused repetitive Ca(2+) release from intracellular Ca(2+) stores resulting in baseline spikes of [Ca(2+)](i). The thimerosal-induced [Ca(2+)](i) oscillations did not change in the presence of PDBu and the phospholipase C inhibitor U73122. Thus, we could not provide evidence that negative feedback by PKC plays a central role in the regulation of ATP-induced [Ca(2+)](i) oscillations. These results suggest that the [Ca(2+)](i) oscillations, at least the baseline spikes, in HSY cells can be generated without stimulating the formation of IP(3).

Adenosine Triphosphate↗
PubMed2000

Route of decomposition of thiomersal (thimerosal).

The route of formation and identification of the principal degradation products of thimerosal (thiomersal) has been undertaken. The initial oxidation to dithiosalicylic acid is followed by cleavage of the disulphide bond of the dithiosalicylic acid by the ethylmercuric ion to reform 1.5 mol of thimerosal with concurrent oxidation to form 0.5 mol of 2-sulfinobenzoic acid for each mole of dithiosalicylic acid. In the presence of copper ions 2-sulfobenzoic acid was also formed. A mechanism has been proposed which accounts for the stoichiometry of the cleavage reaction observed and the significance of the reaction is discussed.

Anti-Infective Agents, Local↗
PubMed1997

Simultaneous determination of methylparaben, propylparaben and thimerosal by high-performance liquid chromatography and electrochemical detection.

A reversed-phase high-performance liquid chromatographic method using amperometric detection has been developed for the analysis of methylparaben, propylparaben and thimerosal. The liquid chromatographic separation of the three preservatives was made possible on a C18-bonded silica column with a mixed solvent consisting of methanol and aqueous 0.02 M phosphoric acid (59:41, v/v). A potential value of +1.25 V versus Ag/AgCl was chosen for simultaneous analysis. The limits of detection were 1, 2 and 5 ng for a 20 microliters injection volume of methylparaben, propylparaben and thimerosal, respectively. The analysis time of less than 20 min in this study was found to be applicable for routine analysis of these compounds in pharmaceutical products.

Chromatography, High Pressure Liquid↗
PubMed2004

Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal.

Methylation events play a critical role in the ability of growth factors to promote normal development. Neurodevelopmental toxins, such as ethanol and heavy metals, interrupt growth factor signaling, raising the possibility that they might exert adverse effects on methylation. We found that insulin-like growth factor-1 (IGF-1)- and dopamine-stimulated methionine synthase (MS) activity and folate-dependent methylation of phospholipids in SH-SY5Y human neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent mechanism. The stimulation of this pathway increased DNA methylation, while its inhibition increased methylation-sensitive gene expression. Ethanol potently interfered with IGF-1 activation of MS and blocked its effect on DNA methylation, whereas it did not inhibit the effects of dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS activity, as well as folate-dependent phospholipid methylation: Cu(2+) promoted enzyme activity and methylation, while Cu(+), Pb(2+), Hg(2+) and Al(3+) were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC(50) of 1 nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggests that it may be an important target of neurodevelopmental toxins.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2006

An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States.

Thimerosal is an ethylmercury (49.55% mercury by weight) preservative historically added to some vaccines. Toxicokinetic studies showed children in the United States received doses of mercury from Thimerosal-containing vaccines (TCVs) in excess of safety guidelines. In the United States during the 1990s, diphtheria-tetanus-pertussis (DTP) and Haemophilus influenzae type b (Hib) vaccines (maximally, 50 mug mercury per joint administration) and diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTPH) vaccines (25 mug mercury per administration) were given to children in the same childhood vaccination schedule at 2, 4, 6, and 15-18 mo, so that children receiving DTP and Hib vaccines may have maximally received an additional 100 mug more mercury exposure from TCVs than children administered DTPH vaccines. A case-control epidemiological study of neurodevelopmental disorders (NDs) reported to the Vaccine Adverse Event Reporting System (VAERS) (online public access version; updated 31 August 2004) following administration of DTP vaccines in comparison DTPH vaccines manufactured by Lederle Laboratories (Pearl River, NY) from 1994 through 1998 was undertaken. Significantly increased odds ratios for autism, speech disorders, mental retardation, infantile spasms, and thinking abnormalities reported to VAERS were found following DTP vaccines in comparison to DTPH vaccines with minimal bias or systematic error. Additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially since in 2005 the Institute of Medicine issued a report calling into question handling of vaccine safety data by the National Immunization Program of the Centers for Disease Control and Prevention.

Bacterial Capsules↗
PubMed1990

Ocular sensitivity to thimerosal: a problem with hepatitis B vaccine?

Strict interpretation of the package insert for hepatitis B vaccine (Heptavax-B and Recombivax HB) would preclude its administration to anyone with a history of ocular sensitivity to thimerosal, but data to support this are hard to find. Given the large number of vaccinees, many of whom wear contact lenses, reported cases of significant adverse reactions are sparse. No studies have directly addressed the ocular sensitivity issue. For two years, we monitored an immunization program for hospital employees. Ten employees (2.2%) gave a history of ocular sensitivity to thimerosal. Nine were vaccinated, without untoward reactions. This small series does not resolve the safety issue and should not be so interpreted. Likewise, the question of danger remains unanswered. If others administering the vaccine would ask the proper questions, sufficient numbers could be generated and reported that would either support the contraindication, or lead to a change in its present wording.

Drug Hypersensitivity↗
PubMed1991

Sensitivity to thimerosal and photosensitivity to piroxicam.

17 patients allergic to thimerosal, with no previous history of photosensitivity or piroxicam ingestion, 2 patients with piroxicam-induced photosensitivity, and 10 controls were patch or photopatch tested, with 1 or more of the following: thimerosal, thiosalicylic acid, irradiated and non-irradiated solutions of piroxicam alone, L-cysteine alone and piroxicam plus L-cysteine, and piroxicam in petrolatum., The results of the tests supported the hypothesis that there are cross-reactions between thiosalicylic acid and prioxicam, a photosensitizer. The mechanism of the cross-reactions may involve photoproducts of piroxicam and L-cysteine, as patients allergic to thiosalicylic acid, who have positive photopatch tests to piroxicam, also had positive patch tests to the irradiated solution of piroxicam plus L-cysteine.

Adult↗
PubMed1996

Hypersensitivity to thimerosal: the sensitizing moiety.

There has been increasing interest in characterizing the sensitizing moiety of thimerosal [TIM], following the finding that patients with photosensitivity to piroxicam are allergic to the thiosalicylic acid [TIO] moiety of TIM. For this purpose, the authors have conducted 2 studies in TIM-sensitive patients. In the 1st, of 175 patients tested with TIO and ammoniated mercuric chloride [HGAM], 45.7% reacted only to TIM, whereas 45.7% reacted also to TIO and 17.7% also to HGAM; 9.1% reacted to both TIO and HGAM. In the 2nd, of 47 patients tested with TIO and ethylmercuric chloride [ETHG], 87.2% reacted to ETHG, 44.7% to TIO and 31.9% reacted to both. None of the patients reacted only to TIM. The authors conclude that thimerosal allergy is due either to the mercuric moiety or to thiosalicylic acid, with no cases of sensitivity only to the whole molecule of TIM. TIM-sensitive patients are mainly allergic to the mercuric moiety, but among them there are a large number of TIO-sensitive patients, and these should be advised to avoid piroxicam.

Adolescent↗
PubMed1998

Thimerosal positivities: the role of organomercury alkyl compounds.

Contact allergy to thimerosal (TH) has not been considered a marker for mercury allergy, since there is a low degree of cross-sensitivity to inorganic as well as to organic mercury salts. 40 subjects, who previously gave a positive patch test reaction only to thimerosal 0.1% pet. (Hermal), when simultaneously repatch-tested to solutions containing TH, mersalyl acid, p-amino-phenylmercuric acid, mercuric acetate and thiosalicylic acid, respectively, gave positive reactions only to TH. 36 out of 40 subjects were divided into 2 groups of 18 subjects and simultaneously repatch-tested to solutions containing TH, methylmercury chloride (MeHgCl), thiosalicylic acid, and, ethylmercury chloride (EtHgCl), respectively. EtHgCl was tested in the 1st group at 0.031% and in the 2nd group at 0.015%. The results showed that all subjects gave concomitant positive reactions to TH, EtHgCl and MeHgCl. EtHgCl 0.031% gave a higher number of reactions than EtHgCl 0.015%, underlining the rôle of the solvent in these reactions. Patch test results in 300 consecutive patients to a standard series, to which MeHgCl was added, showed that MeHgCl and TH were never able to give isolated positive reactions, and that the concomitant positive reactions occurred in only 3.6% of subjects. In conclusion, our data seem to suggest that the positive reactions to TH found in our patients were due to EtHgCl, and that the structural similarities with MeHgCl were so close that the skin reacted against each as if they were identical.

Alkylation↗
PubMed2000

Update: expanded availability of thimerosal preservative-free hepatitis B vaccine.

Thimerosal, a mercury-based compound, is no longer used as a preservative in any of the pediatric hepatitis B vaccines licensed in the United States. On March 28, 2000, SmithKline Beecham Biologicals (Rixensart, Belgium) received approval from the Food and Drug Administration of a supplement to its hepatitis B license to include the manufacture of single-antigen, preservative-free hepatitis B vaccine (Engerix-B, pediatric/adolescent); distribution of this product has begun. A single-antigen, preservative-free hepatitis B vaccine (Recombivax HB, pediatric) from Merck Vaccine Division (West Point, Pennsylvania) had earlier received similar approval (1). A preservative-free Haemophilus influenzae type b (Hib)/hepatitis B combination vaccine (Comvax) from Merck Vaccine Division also is available. An adequate supply of preservative-free hepatitis B vaccine is available for all infant and childhood vaccinations. Thimerosal preservative-containing hepatitis B vaccines may continue to be used for vaccination of adolescents and adults as recommended (2).

Hepatitis B Vaccines↗